Antineoplastics

Abstract

Development of resistance in non-small-cell lungcancer : 21 case reports In a retrospective study (study period: between May 2003 and December 2016) of 27 patients, 21 patients [ages and sexes not stated] were described, who developed resistance to afatinib, erlotinib, gefitinib or platinum-based unspecified chemotherapy, indicated for lung adenocarcinoma (n=20) or lung adeno squamous cancer (n=1). Among the 21 patients, one patient had an off-label use of third-line afatinib [dosages and routes not stated; not all durations of treatments to reactions onsets and outcomes stated]. The patients had underlying lung adenocarcinoma (n=20) or lung adeno squamous cancer (n=1) with baseline EGFR mutation at 19del, 19del /T790M, 19del/19del, L858R or 19del T790M. The patients started receiving first-line afatinib (2 patients), first-line gefitinib (11 patients), second-line gefitinib (3 patients), first-line erlotinib (2 patients; between the two patients one received third-line platinum-based chemotherapy additionally), second-line erlotinib (1 patient), third-line erlotinib (1 patient) or second-line erlotinib and offlabel third line afatinib (1 patient). Progression-free survival ranged between 4–76 months [not all aetiology stated]. Thereafter, the patients underwent biopsy at the peritoneum, lung, pleura, upper-right lobe of lung, lower-right lobe of lung, lymph node, kidney, pleural effusion site, node or liver. In the 21 patients, biopsy findings revealed T790M positive mutation (n=12), T790M discordance (n=1), T790M concordance (n=1), MET amplification (n=2), development of small cell lung cancer (SCLC; n=3) or T790M negative (n=2). Re-biopsies were carried out in four of the 21 patients (1 patient with T790M mutation, 1 patient with SCLC and 2 patients with T790 negative finding) at the peritoneum, lung or adrenal gland; among these 4 patients, two patients who underwent re-biopsy and had T790 negative finding, one received off-label third line afatinib following which T790M gain was evident, and in the other patient T790M positive mutation could be found. In the remaining 2 patients out of these 4 patients, T790M positive mutation reversed to T790M negative (1 patient) or SCLC reversed to lung adenocarcinoma (1 patient) after administration of unspecified chemotherapy (third-line). Author comment: [T]he disease resurfaces in a TKIresistant form that is mainly linked to an acquired EGFRT790M mutation, a MET amplification, or small cell lung cancer (SCLC) transformation. [A]fatinib as an off-label third line option that produced the appearance of a T790M mutation.